Ergothioneine is asulfur-containing histidine derivative that emerges from microbial biosynthesis and enters the human body through intestinal uptake and regulated distribution into specific tissues.A lthough the proteins involved in biosynthesis and uptake are well characterized,l ess is known aboutt he degradative pathways of ergothioneine. This report describes the crystal structure of the active form of ergothionasef rom the oral pathogen Treponemad enticola complexed with the substrate analogued esmethyl-ergothioneine sulfonica cid. This enzyme catalyzes the 1,2-elimination of trimethylamine from ergothioneine and ergothioneine sulfonic acid by using au nique mode of substrate activation combined with acid/base catalysis. This structural and mechanistic investigation revealed four essential catalytic residues, which are strictly conserved in homologous proteins from common gastrointestinal bacteria and numerous pathogenic bacteria, suggesting that bacterial activity mayp lay an important role in determining the availability of ergothioneine in healthy and diseased human tissue. Figure 3.To p: Proposed substrate binding mode and mechanism for substrate activationbyTdETL wt .Bottom:Chargec omplementary enzyme:ligand complexes that stabilize ap ositivec harge on the imidazole ring (green)a re more active that complexes with unbalanced chargeo ran eutral imidazole ring (red). Bold letters indicate the corresponding entries in Ta ble 1.
Coenzyme A (CoA) is a common cofactor in biochemical reactions, and CoA‐dependent enzymes catalyze essential steps in anabolism and catabolism. This complex molecule also plays an important role in the synthesis of many high‐value products, such as synthetic antibiotics, vitamins, pheromones, and biopolymers. Nevertheless, the synthetic potential for biocatalytic processes cannot be fully exploited owing to the lack of an efficient regeneration system. Here, we report an acyl‐CoA regeneration system with integrated adenosine triphosphate (ATP) regeneration that is based on inexpensive polyphosphate as the single energy source. In the four‐enzyme cascade, two cofactors, acyl‐CoA and ATP, are each regenerated up to 2000 times. The applicability for different acyl donors and acceptors is shown by HPLC analysis. Owing to its flexibility toward virtually all relevant substrates, the system has the potential to make CoA‐dependent reactions more accessible for chemical synthesis in vitro.
Ergothioneine has emerged as a crucial cytoprotectant in the pathogenic lifestyle of Mycobacterium tuberculosis. Production of this antioxidant from primary metabolites may be regulated by phosphorylation of Thr213 in the active site of the methyltransferase EgtD. The structure of mycobacterial EgtD suggests that this post-translational modification would require a large-scale change in conformation to make the active-site residue accessible to a protein kinase. In this report, we show that, under in vitro conditions, EgtD is not a substrate of protein kinase PknD.
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